Correlation-based network integration of lung RNA sequencing and DNA methylation data in chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous, chronic inflammatory process of the lungs and, like other complex diseases, is caused by both genetic and environmental factors. Detailed understanding of the molecular mechanisms of complex diseases requires the study of the interplay among different biomolecular layers, and thus the integration of different omics data types. In this study, we investigated COPD-associated molecular mechanisms through a correlation-based network integration of lung tissue RNA-seq and DNA methylation data of COPD cases (n = 446) and controls (n = 346) derived from the Lung Tissue Research Consortium. First, we performed a SWIM-network based analysis to build separate correlation networks for RNA-seq and DNA methylation data for our case-control study population. Then, we developed a method to integrate the results into a coupled network of differentially expressed and differentially methylated genes to investigate their relationships across both molecular layers. The functional enrichment analysis of the nodes of the coupled network revealed a strikingly significant enrichment in Immune System components, both innate and adaptive, as well as immune-system component communication (interleukin and cytokine-cytokine signaling). Our analysis allowed us to reveal novel putative COPD-associated genes and to analyze their relationships, both at the transcriptomics and epigenomics levels, thus contributing to an improved understanding of COPD pathogenesis.

The association and underlying mechanism of the digit ratio (2D:4D) in hypospadias.

ABSTRACT: The second-to-fourth digit (2D:4D) ratio is thought to be associated with prenatal androgen exposure. However, the relationship between the 2D:4D ratio and hypospadias is poorly understood, and its molecular mechanism is not clear. In this study, by analyzing the hand digit length of 142 boys with hypospadias (23 distal, 68 middle, and 51 proximal) and 196 controls enrolled in Shanghai Children's Hospital (Shanghai, China) from December 2020 to December 2021, we found that the 2D:4D ratio was significantly increased in boys with hypospadias (P < 0.001) and it was positively correlated with the severity of the hypospadias. This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene (dynein axonemal heavy chain 8 [DNAH8]) associated with hypospadias. Furthermore, the discrepancy was mainly caused by a shift in 4D. Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D. Comprehensive mechanistic explorations revealed that during the androgen-sensitive window, the downregulation of the androgen receptor (AR) caused by low testosterone levels, as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a (Wnt5a), Wnt5b, Smad family member 2 (Smad2), and Smad3; mitochondrial function-related genes in cartilage such as AMP-activated protein kinase (AMPK) and nuclear respiratory factor 1 (Nrf-1); and vascular development-related genes such as myosin light chain (MLC), notch receptor 3 (Notch3), and sphingosine kinase 1 (Sphk1), are responsible for the limitation of 4D growth, which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification. This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

Arresting the bad seed: HDAC3 regulates proliferation of different microglia after ischemic stroke.

The accumulation of self-renewed polarized microglia in the penumbra is a critical neuroinflammatory process after ischemic stroke, leading to secondary demyelination and neuronal loss. Although known to regulate tumor cell proliferation and neuroinflammation, HDAC3's role in microgliosis and microglial polarization remains unclear. We demonstrated that microglial HDAC3 knockout (HDAC3-miKO) ameliorated poststroke long-term functional and histological outcomes. RNA-seq analysis revealed mitosis as the primary process affected in HDAC3-deficent microglia following stroke. Notably, HDAC3-miKO specifically inhibited proliferation of proinflammatory microglia without affecting anti-inflammatory microglia, preventing microglial transition to a proinflammatory state. Moreover, ATAC-seq showed that HDAC3-miKO induced closing of accessible regions enriched with PU.1 motifs. Overexpressing microglial PU.1 via an AAV approach reversed HDAC3-miKO-induced proliferation inhibition and protective effects on ischemic stroke, indicating PU.1 as a downstream molecule that mediates HDAC3's effects on stroke. These findings uncovered that HDAC3/PU.1 axis, which mediated differential proliferation-related reprogramming in different microglia populations, drove poststroke inflammatory state transition, and contributed to pathophysiology of ischemic stroke.

Adherence to dietary guidelines associated with lower medical service utilization in preschoolers: a longitudinal study.

OBJECTIVE: We aimed to evaluate the association between dietary guideline adherence and overall, outpatient, and emergency medical service utilization in Taiwanese preschoolers. METHODS: We selected 614 preschoolers (2-6 years) who had one day of 24-h dietary recall data from the 2013-2016 Nutrition and Health Survey in Taiwan. The Taiwanese Children Healthy Eating Index (TCHEI) was developed on the basis of Taiwanese Food-Based Dietary Guidelines; it assesses dietary adequacy and eating behavior. Data on the participants' outpatient and emergency medical service utilization were obtained for 2013-2018 from the National Health Insurance Research Database. A multivariable generalized linear model was used to evaluate the association between the TCHEI and medical service utilization for all disease and respiratory diseases. RESULTS: After adjustment for confounding factors, children aged 2-3 years in the Tertile (T) 2 and T3 groups of the TCHEI exhibited 25% (95% CI 0.69-0.83) and 16% (95% CI 0.77-0.92) lower overall medical visits, respectively. The same pattern was noted in the outpatient and emergency visits for all diseases and respiratory diseases. The children aged 4-6 years in the T2 group exhibited 15% (95% CI 0.80-0.91) and 11% (95% CI 0.82-0.97) lower overall visits and visits for respiratory diseases, respectively. Moreover, preschoolers in the T2 group exhibited lower overall medical expenditures than did those in the T1 group. CONCLUSIONS: TCHEI score was positively correlated with better nutritional status. Optimal dietary intake associated with lower medical service utilization among Taiwan preschoolers.

For the penile length-how shall we choose the straightening procedures in hypospadias repair?

OBJECTIVE: To define the appropriate penile straightening procedures corresponding to the specific penile curvature by comparing the penile length resulting from various straightening procedures in hypospadias repair. METHODS: We retrospectively analyzed hypospadias patients between 2017 and 2019. Patients were divided into three groups based on the penile curvature after degloving: <30°, 30°-45°, and >45°. The penile straightening procedures include dorsal plication (DP), simple urethral plate (UP) transection, and UP transection with ventral lengthening (VL). The paired t-test was conducted for the penile length after fully straightening in each group, simultaneously calculating the length changes (∆T). In addition, the penile length changes among these procedures were compared using Spearman analysis to show the correlation between the penile curvature and the length. RESULTS: The penile length changed significantly after fully straightening in all groups. The length decreased mildly after DP, while increased in the other procedures. The penile curvature after degloving was positively correlated with the absolute change in the penile length (P < 0.001, r = 0.424) and the ratio of ∆T in the original length (P < 0.001, r = 0.433). CONCLUSION: For hypospadias, the 30° after degloving may serve as the cut-off for the selection of the straightening method from the perspective of the penile length. For those with < 30°, methods such as DP or UP transection can either be selected. In patients with > 30°, DP should be used with caution because of the potential risk to shorten the penis. In contrast, UP transection effectively corrects the penile curvature and increases the penile length concurrently, which should be primarily recommended in those patients.

A solid-state electrolyte for electrochemical lithium-sulfur cells.

Post-lithium-ion batteries are designed to achieve high energy density and high safety by modifying their active material and cell configuration. In terms of the active material, lithium-sulfur batteries have the highest charge-storage capacity and high active-material utilization because of the use of a conversion-type sulfur cathode, which involves conversion between solid-state sulfur, liquid-state polysulfides, and solid-state sulfides. In terms of the configuration, solid-state batteries ensure high safety by using a solid-state electrolyte in between the two electrodes. Herein, we use a lithium lanthanum titanate (LLTO) solid-state electrolyte in the lithium-sulfur cell with a polysulfide catholyte electrode. The LLTO, which replaces the conventional liquid electrolyte, is a solid-state electrolyte that offers smooth lithium-ion diffusion and prevents the loss of polysulfides, while the highly active polysulfide electrode, which replaces the solid-state sulfur cathode, improves the reaction kinetics and the active-material utilization. The material and electrochemical analyses confirm the stabilized electrodes exhibit long-lasting lithium stripping/plating stability and limited polysulfide diffusion. Moreover, the morphologically and electrochemically smooth interface between the solid-state electrolyte and catholyte enables fast charge transfer in the cell, which demonstrates a high charge-storage capacity of 1429 mA h g-1, high rate performance, and high electrochemical efficiency.

Age-dependent effects of acute stress on the behavior, blood parameters, immunity, and enteric nerves of mice.

The impact of stress on mental and digestive health has been extensively studied, with chronic stress being associated with various disorders. However, age-related differences in the response to acute stress, both behaviorally and physiologically, remain poorly understood. Therefore, this study aimed to develop a model to detect transient stress in mice of different ages. The stressor employed in our experiments was a restraint stress procedure, where mice were subjected to brief periods of immobilization to induce an acute stress response. Male C3H/HeN mice aged 3, 6, 12, and 30 weeks were subjected to acute restrain stress (ARS) by being placed in a 50 ml conical centrifuge tube for 15 min. Subsequently, their behavior, organ tissues, hematological parameters, cortisol concentration, and immune responses were assessed. Following ARS, the increased in time and entries into the center by the 12-week-old mice following stress. In comparison to mice of other ages, those aged 6 weeks demonstrated notable elevations in erythrocytes, platelets, hemoglobin, and hematocrit, all of which were influenced by the time-dependent changes and the recovery process of ARS. Blood corticosterone levels were substantially elevated in all age groups after ARS. Furthermore, ARS induced a notable increase in leukocytes, basophils, residential macrophages, and CD4+ T cells in all age groups except for 3-week-old mice. However, the number of monocyte-derived macrophages and CD8+ T cells did not change significantly. Additionally, mice aged 3 and 6 weeks demonstrated an increase in GFAP+ cells following ARS, whereas NeuN+ cells decreased across all ages. These results suggest that ARS has varying effects on the behavior, cortisol concentration, and quantity of blood cells as well as hepatic immune cells in mice of different ages. These age-dependent responses shed light on the complex interplay between stress and physiological systems and contribute to the broader understanding of stress-related diseases.

Urethro-urethrostomy for urethral duplication (Type IIA1) in a 3-years-old boy: Surgical approach.

INTRODUCTION: To report a novel maneuver of end-to-side urethro-urethrostomy for managing Type IIA1 urethral duplication (UD). MATERIALS AND METHODS: A 3-years-old boy was referred to our institute for abnormal appearance of genitalia. Physical examination revealed an epispadiac meatus on the dorsum of the penile shaft, in addition to the orthotopic meatus at the tip of glans. He can void through both urethrae with continence (grade I). Voiding cystourethrography and the cystoscopy confirmed the Type IIA1 UD with two urethrae arising independently from the bladder neck. A novel maneuver of end-to-side urethro-urethrostomy transferring the dorsal urethra through the corpus cavernosa and anastomosing it to the posterior wall of the ventral urethra was successfully performed. RESULTS: The urethral catheter was removed 2 weeks postoperatively. Neither urethral stricture nor fistula was noticed. After 1 year of followed-up, the boy can void fluently with continence (grade I). The Qmax was 10.4 ml/s. CONCLUSION: Our maneuver of end-to-side urethro-urethrostomy for managing Type IIA1 UD was safe and effective, especially for the continent cases with the ectopic meatus on the penile shaft.

Insight into coagulation/flocculation mechanisms on microalgae harvesting by ferric chloride and polyacrylamide in different growth phases.

FeCl3 and polyacrylamide (PAM) had been used to investigate the effect of coagulation, flocculation, and their combination on algae cells and extracellular organic matter (EOM) at different phases. PAM tended to aggregate particle-like substances, while FeCl3 could interact with EOM. The content of EOM kept rising during the algae growth cycle, while OD680 peaked at about 3.0. At stationary phase Ⅰ, the removal efficiencies of UV254, turbidity and OD680 of the suspension conditioned with FeCl3 + PAM reached (88.08 ± 0.89)%, (89.72 ± 0.36)% and (93.99 ± 0.05)%, respectively. Nevertheless, PAM + FeCl3 exhibited the worst efficiency because of the release of EOM caused by the turbulence. The results suggested that algal cells served as a coagulation aid to facilitate floc formation, while excessive EOM deteriorated harvesting performance. The process of FeCl3 + PAM at stationary phase Ⅰ appears to be a promising technology for microalgae harvesting.

Microglial histone deacetylase 2 is dispensable for functional and histological outcomes in a mouse model of traumatic brain injury.

The Class-I histone deacetylases (HDACs) mediate microglial inflammation and neurological dysfunction after traumatic brain injury (TBI). However, whether the individual Class-I HDACs play an indispensable role in TBI pathogenesis remains elusive. HDAC2 has been shown to upregulate pro-inflammatory genes in myeloid cells under brain injuries such as intracerebral hemorrhage, thereby worsening outcomes. Thus, we hypothesized that HDAC2 drives microglia toward a pro-inflammatory neurotoxic phenotype in a murine model of controlled cortical impact (CCI). Our results revealed that HDAC2 expression was highly induced in CD16/CD32+ pro-inflammatory microglia 3 and 7d after TBI. Surprisingly, microglia-targeted HDAC2 knockout (HDAC2 miKO) mice failed to demonstrate a beneficial phenotype after CCI/TBI compared to their wild-type (WT) littermates. HDAC2 miKO mice exhibited comparable levels of grey and white matter injury, efferocytosis, and sensorimotor and cognitive deficits after CCI/TBI as WT mice. RNA sequencing of isolated microglia 3d after CCI/TBI indicated the elevation of a panel of pro-inflammatory cytokines/chemokines in HDAC2 miKO mice over WT mice, and flow cytometry showed further elevated brain infiltration of neutrophils and B cells in HDAC2 miKO mice. Together, this study does not support a detrimental role for HDAC2 in microglial responses after TBI and calls for investigation into alternative mechanisms.

Preconditioning of exosomes derived from human olfactory ensheathing cells improved motor coordination and balance in an SCA3/MJD mouse model: A new therapeutic approach.

Exosome therapy is a novel trend in regeneration medicine. However, identifying a suitable biomarker that can associate the therapeutic efficacy of exosomes with SCA3/MJD is essential. In this study, parental cells were preconditioned with butylidenephthalide (Bdph) for exosome preparation to evaluate the therapeutic effect of SCA3/MJD. The therapeutic agent hsa-miRNA-6780-5p was enriched up to 98-fold in exosomes derived from butylidenephthalide (Bdph)-preconditioned human olfactory ensheathing cells (hOECs) compared with that in naïve hOECs exosomes. The particle sizes of exosomes derived from naïve hOECs and those derived from hOECs preconditioned with Bdph were approximately 113.0 ± 3.5 nm and 128.9 ± 0.7 nm, respectively. A liposome system was used to demonstrate the role of hsa-miRNA-6780-5p, wherein hsa-miRNA-6780-5p was found to enhance autophagy and inhibit the expression of spinocerebellar ataxia type 3 (SCA3) disease proteins with the polyglutamine (polyQ) tract. Exosomes with enriched hsa-miRNA-6780-5p were further applied to HEK-293-84Q cells, leading to decreased expression of polyQ and increased autophagy. The results were reversed when 3MA, an autophagy inhibitor, was added to the cells treated with hsa-miRNA-6780-5p-enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. SCA3 mice showed improved motor coordination behavior when they intracranially received exosomes enriched with hsa-miRNA-6780-5p. SCA3 mouse cerebellar tissues treated with hsa-miRNA-6780-5p-enriched exosomes showed decreased expression of polyQ and increased expression of LC3II/I, an autophagy marker. In conclusion, our findings can serve as a basis for developing an alternative therapeutic strategy for SCA3 disease treatment using miRNA-enriched exosomes derived from chemically preconditioned cells.

ASK1-K716R reduces neuroinflammation and white matter injury via preserving blood-brain barrier integrity after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a significant worldwide public health concern that necessitates attention. Apoptosis signal-regulating kinase 1 (ASK1), a key player in various central nervous system (CNS) diseases, has garnered interest for its potential neuroprotective effects against ischemic stroke and epilepsy when deleted. Nonetheless, the specific impact of ASK1 on TBI and its underlying mechanisms remain elusive. Notably, mutation of ATP-binding sites, such as lysine residues, can lead to catalytic inactivation of ASK1. To address these knowledge gaps, we generated transgenic mice harboring a site-specific mutant ASK1 Map3k5-e (K716R), enabling us to assess its effects and elucidate potential underlying mechanisms following TBI. METHODS: We employed the CRIPR/Cas9 system to generate a transgenic mouse model carrying the ASK1-K716R mutation, aming to investigate the functional implications of this specific mutant. The controlled cortical impact method was utilized to induce TBI. Expression and distribution of ASK1 were detected through Western blotting and immunofluorescence staining, respectively. The ASK1 kinase activity after TBI was detected by a specific ASK1 kinase activity kit. Cerebral microvessels were isolated by gradient centrifugation using dextran. Immunofluorescence staining was performed to evaluate blood-brain barrier (BBB) damage. BBB ultrastructure was visualized using transmission electron microscopy, while the expression levels of endothelial tight junction proteins and ASK1 signaling pathway proteins was detected by Western blotting. To investigate TBI-induced neuroinflammation, we conducted immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry analyses. Additionally, immunofluorescence staining and electrophysiological compound action potentials were conducted to evaluate gray and white matter injury. Finally, sensorimotor function and cognitive function were assessed by a battery of behavioral tests. RESULTS: The activity of ASK1-K716R was significantly decreased following TBI. Western blotting confirmed that ASK1-K716R effectively inhibited the phosphorylation of ASK1, JNKs, and p38 in response to TBI. Additionally, ASK1-K716R demonstrated a protective function in maintaining BBB integrity by suppressing ASK1/JNKs activity in endothelial cells, thereby reducing the degradation of tight junction proteins following TBI. Besides, ASK1-K716R effectively suppressed the infiltration of peripheral immune cells into the brain parenchyma, decreased the number of proinflammatory-like microglia/macrophages, increased the number of anti-inflammatory-like microglia/macrophages, and downregulated expression of several proinflammatory factors. Furthermore, ASK1-K716R attenuated white matter injury and improved the nerve conduction function of both myelinated and unmyelinated fibers after TBI. Finally, our findings demonstrated that ASK1-K716R exhibited favorable long-term functional and histological outcomes in the aftermath of TBI. CONCLUSION: ASK1-K716R preserves BBB integrity by inhibiting ASK1/JNKs pathway in endothelial cells, consequently reducing the degradation of tight junction proteins. Additionally, it alleviates early neuroinflammation by inhibiting the infiltration of peripheral immune cells into the brain parenchyma and modulating the polarization of microglia/macrophages. These beneficial effects of ASK1-K716R subsequently result in a reduction in white matter injury and promote the long-term recovery of neurological function following TBI.

Clopidogrel-Related High Residual Platelet Reactivity Associated with Estimated Glomerular Filtration Rate in Patients with Acute Ischemic Stroke.

INTRODUCTION: There are few studies on the relationship between the occurrence of clopidogrel-related high residual platelet reactivity (HRPR) and estimated glomerular filtration rate (eGFR) at admission in patients with ischemic stroke. The aim of this study was to investigate the possible relationship between the two. METHODS: Patients who were hospitalized and diagnosed with acute ischemic stroke were recruited from July 1, 2017, to June 30, 2018, at Shanghai TCM-Integrated Hospital. Renal function was measured within 24 h of enrollment and eGFR was calculated. Patients were tested for platelet reactivity using the VerifyNow system after 7 days of antiplatelet therapy with clopidogrel 75 mg/d alone, and patients with P2Y12 reaction unit values ≥230 were diagnosed with HRPR. The association between HRPR and eGFR was analyzed. RESULTS: A total of 274 patients were enrolled in the study, of whom 91 (33.21%) had HRPR. Multivariate logistic regression analysis suggested that an increased risk of HRPR was independently associated with female sex and reduced eGFR (female sex: OR = 2.24, 95% CI: 1.26-3.99, p = 0.006; mild chronic kidney disease [CKD]: OR = 2.95, 95% CI: 1.47-5.93, p = 0.002; moderate CKD: OR = 3.07, 95% CI: 1.08-8.75, p = 0.04). CONCLUSION: Decreased eGFR is an independent risk factor for the occurrence of HRPR in patients with ischemic stroke.

Genomic and phenotypic-based safety assessment and probiotic properties of Streptococcus thermophilus FUA329, a urolithin A-producing bacterium of human milk origin.

Streptococcus thermophilus FUA329, a urolithin A-producing bacterium, is isolated from human breast milk. The complete genome sequence of FUA329 did not contain any plasmids and at least 20 proteins were related to extreme environment resistance. Phenotypic assay results demonstrated that FUA329 was susceptible to 12 kinds of antibiotics and did not exhibit any hemolytic or nitrate reductase activity. Three free radical scavenging assays revealed that FUA329 have high antioxidant capability. FUA329 exhibited a cell surface hydrophobicity of 52.58 ± 1.17% and an auto-aggregation rate of 18.69 ± 2.48%. Moreover, FUA329 demonstrated a survival rate of over 60% in strong acid and bile salt environments, indicating that FUA329 may be stable colonization in the gastrointestinal tract. Additionally, we firstly found 3 potential proteins and 11 potential genes of transforming ellagic acid to urolithins in FUA329 genome. The above results indicate that FUA329 has credible safety and probiotic properties, as well as the potential to be developed as a new generation of urolithin A-producing probiotics.

Engineering pedicled vascularized bladder tissue for functional bladder defect repair.

An engineered bladder construct that mimics the structural and functional characteristics of native bladder is a promising therapeutic option for bladder substitution. We previously showed that pedicled vascularized smooth muscle tissue fabricated by grafting smooth muscle cell (SMC) sheets onto an axial capsule vascular bed had the potential for reliable bladder reconstruction. In this study, we investigated the feasibility of buccal mucosa graft (BMG) integration with the pedicled vascularized smooth muscle tissue to generate a full-layer pedicled vascularized bladder construct. BMG transplanted onto vascularized smooth muscle tissue showed good survival and developed into a pedicled vascularized bladder construct with full-layer structures, appropriate thickness, abundant vascularization, and effective barrier function. Then the full-thickness bladder defects were, respectively, reconstructed by pedicled capsule tissue (pedicled capsule group), nonpedicled vascularized bladder construct (nonpedicled construct group), and pedicled vascularized bladder construct (pedicled construct group). The picrosirius red (PSR) staining and immunohistochemistry results showed minimal fibrosis, maximal smooth muscle proportion, and high vascular density in the pedicled construct group. A continuous mucosal layer was observed only in the pedicled construct group. Moreover, morphological and functional studies revealed better bladder compliance and good ductility in the pedicled construct group. Overall, these results suggested that the BMG could be well integrated with vascularized smooth muscle tissue and generated a pedicled, fully vascularized, and structurally organized bladder construct, which facilitated structural remodeling and functional recovery and could become an alternative to bladder reconstruction.

The Influence of Glenoid Bone Loss and Graft Positioning on Graft and Cartilage Contact Pressures After the Latarjet Procedure.

BACKGROUND: Glenohumeral joint contact loading before and after glenoid bone grafting for recurrent anterior instability remains poorly understood. PURPOSE: To develop a computational model to evaluate the influence of glenoid bone loss and graft positioning on graft and cartilage contact pressures after the Latarjet procedure. STUDY DESIGN: Controlled laboratory study. METHODS: A finite element model of the shoulder was developed using kinematics, muscle and glenohumeral joint loading of 6 male participants. Muscle and joint forces at 90° of abduction and external rotation were calculated and employed in simulations of the native shoulder, as well as the shoulder with a Bankart lesion, 10% and 25% glenoid bone loss, and after the Latarjet procedure. RESULTS: A Bankart lesion as well as glenoid bone loss of 10% and 25% significantly increased glenoid and humeral cartilage contact pressures compared with the native shoulder (P < .05). The Latarjet procedure did not significantly increase glenoid cartilage contact pressure. With 25% glenoid bone loss, the Latarjet procedure with a graft flush with the glenoid and the humerus positioned at the glenoid half-width resulted in significantly increased humeral cartilage contact pressure compared with that preoperatively (P = .023). Under the same condition, medializing the graft by 1 mm resulted in humeral cartilage contact pressure comparable with that preoperatively (P = .097). Graft lateralization by 1 mm resulted in significantly increased humeral cartilage contact pressure in both glenoid bone loss conditions (P < .05). CONCLUSION: This modeling study showed that labral damage and greater glenoid bone loss significantly increased glenoid and humeral cartilage contact pressures in the shoulder. The Latarjet procedure may mitigate this to an extent, although glenoid and humeral contact loading was sensitive to graft placement. CLINICAL RELEVANCE: The Latarjet procedure with a correctly positioned graft should not lead to increased glenohumeral joint contact loading. The present study suggests that lateral graft overhang should be avoided, and in the situation of large glenoid bone defects, slight medialization (ie, 1 mm) of the graft may help to mitigate glenohumeral joint contact overloading.

HSPB2 facilitates neural regeneration through autophagy for sensorimotor recovery after traumatic brain injury.

Autophagy is a promising target for promoting neural regeneration, which is essential for sensorimotor recovery following traumatic brain injury (TBI). Whether neuronal heat shock protein B2 (HSPB2), a small molecular heat shock protein, reduces injury and promotes recovery following TBI remains unclear. In this study, we demonstrated that HSPB2 was significantly increased in the neurons of a TBI mouse model, patients, and primary neuron cultures subjected to oxygen/glucose deprivation and reperfusion treatment. Upon creating a tamoxifen-induced neuron-specific HSPB2 overexpression transgenic mouse model, we found that elevated HSPB2 levels promoted long-term sensorimotor recovery and alleviated tissue loss after TBI. We also demonstrated that HSPB2 enhanced white matter structural and functional integrity, promoted central nervous system (CNS) plasticity, and accelerated long-term neural remodeling. Moreover, we found that autophagy occurred around injured brain tissues in patients, and the pro-regenerative effects of HSPB2 relied on its autophagy-promoting function. Mechanistically, HSPB2 may regulate autophagy possibly by forming the HSPB2/BCL2-associated athanogene 3/sequestosome-1 complex to facilitate the clearance of erroneously accumulated proteins in the axons. Treatment with the autophagy inhibitor chloroquine during the acute stage or delayed induction of HSPB2 remarkably impeded HSPB2's long-term reparative function, indicating the importance of acute-stage autophagy in long-term neuro-regeneration. Our findings highlight the beneficial role of HSPB2 in neuro-regeneration and functional recovery following acute CNS injury, thereby emphasizing the therapeutic potential of autophagy regulation for enhancing neuro-regeneration.

Immediate CT change after thrombectomy predicting symptomatic hemorrhagic transformation.

BACKGROUND: The prognostic value of contrast accumulation from noncontrast brain computed tomography (CT) conducted immediately after intra mechanical thrombectomy (MT) in patients with acute ischemic stroke to predict symptomatic hemorrhage was studied. METHODS: Patients with acute ischemic stroke treated using MT between February 2015 and April 2019 were included. Contrast accumulation was defined as a high attenuation area observed on noncontrast brain CT conducted immediately after thrombectomy treatment, and the patients were categorized into (1) symptomatic hemorrhage, (2) asymptomatic hemorrhage, and (3) no hemorrhage according to the presence of hemorrhagic transformation and their clinical conditions. The pattern and extent of contrast accumulation were compared between patients with and without symptomatic hemorrhage. The maximal Hounsfield unit (HU) of cortical involvement in contrast accumulation was evaluated by calculating the sensitivity, specificity, odds ratio, and area under the receiver operating characteristic (ROC) curve. RESULTS: In total, 101 patients with anterior circulation acute ischemic stroke were treated by endovascular intervention. Nine patients developed symptomatic hemorrhage and 17 developed asymptomatic hemorrhage. Contrast accumulation was associated with all types of hemorrhagic transformation ( p < 0.01), and cortical involvement pattern was more frequently associated with symptomatic hemorrhage ( p < 0.01). The area under the ROC curve was 0.887. The sensitivity and specificity for HU > 100 in cortical involvement predicting symptomatic hemorrhage after endovascular treatment were 77.8% and 95.7%, respectively, with an odds ratio of 77.0 (95% CI, 11.94-496.50; p < 0.01). CONCLUSION: Cortical involvement of contrast accumulation with a maximal HU > 100 predicts symptomatic hemorrhage after endovascular reperfusion treatment.

Ipsilateral and contralateral patent processus vaginalis in pediatric patients with a unilateral nonpalpable testis.

This study aimed to investigate the incidence of patent processus vaginalis (PPV) in pediatric patients with a unilateral nonpalpable testis and explore the associated factors. From May 2014 to April 2017, 152 boys who were diagnosed with a unilateral nonpalpable testis and underwent laparoscopy in Shanghai Children's Hospital (Shanghai, China) were included in this study. The data were collected and reviewed, and the results were analyzed regarding the age at operation, side, development, and position of the nonpalpable testis. The mean age of the patients was 2.6 (standard deviation: 2.3) years. The testis was absent in 14 cases, nonviable in 81 cases, and viable in 57 cases. The incidence of PPV was 37.5% (57 of 152) on the ipsilateral side and 16.4% (25 of 152) on the contralateral side. The ipsilateral PPV was more prevalent when the nonpalpable testis occurred on the right side ( P < 0.01). Besides, patients with a viable testis had a greater incidence of ipsilateral PPV than those with a nonviable or absent testis ( P < 0.01). Moreover, this rate was the highest when the testis was in the abdominal cavity and the lowest when the testis was in the scrotum (both P < 0.01). However, the incidence of contralateral PPV was independent of all the factors. In conclusion, in children with a nonpalpable testis, the incidence of an ipsilateral PPV was significantly related to the side, development, and position of the testis, while it was independent of these factors on the contralateral side.